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Mutations in Fused-in-Sarcoma (FUS) gene involving the nuclear localization signal (NLS) domain lead to juvenile-onset Amyotrophic Lateral Sclerosis (ALS). The mutant protein mislocalizes to the cytoplasm, incorporating it into Stress Granules (SG). Whether SGs are the first step to the formation of stable FUS-containing aggregates is still unclear. In this work, we used acute and chronic stress paradigms to study the SG dynamics in a human SH-SY5Y neuroblastoma cell line carrying a deletion of the NLS domain of the FUS protein (homozygous ΔNLS-/-; heterozygous ΔNLS+/-). Wild-type (WT) cells served as controls. We evaluated the subcellular localization of the mutant protein through immunoblot and immunofluorescence, in basal conditions and after acute stress and chronic stress with sodium arsenite (NaAsO2). Cells were monitored for up to 24 h after rescue. FUS was expressed in both nucleus and cytoplasm in the ΔNLS+/- cells, whereas it was primarily cytoplasmic in the ΔNLS-/-. Acute NaAsO2 exposure induced SGs at rescue,>90% of ΔNLS cells showed abundant FUS-containing if compared to less than 5% of the WT cells. The proportion of FUS-positive SGs remained 15-20% at 24 h in mutant cells. Cycloheximide did not abolish the long-lasting SGs in mutant cells. Chronic exposure to NaAsO2 did not induce significant SGs formation. A wealth of research has demonstrated that ALS-associated FUS mutations at the C-terminus facilitate the incorporation of the mutant protein into SGs. We have shown here that mutant FUS-containing SGs tend to fail to dissolve after stress, facilitating a liquid-to-solid phase transition. The FUS-containing inclusions seen in the dying motor neurons might therefore directly derive from SGs. This might represent an attractive target for future innovative therapies.The representation of the natural-density, heterogeneous connectivity of neuronal network models at relevant spatial scales remains a challenge for Computational Neuroscience and Neuromorphic Computing. In particular, the memory demands imposed by the vast number of synapses in brain-scale network simulations constitute a major obstacle. Limiting the number resolution of synaptic weights appears to be a natural strategy to reduce memory and compute load. In this study, we investigate the effects of a limited synaptic-weight resolution on the dynamics of recurrent spiking neuronal networks resembling local cortical circuits and develop strategies for minimizing deviations from the dynamics of networks with high-resolution synaptic weights. Selleck KYA1797K We mimic the effect of a limited synaptic weight resolution by replacing normally distributed synaptic weights with weights drawn from a discrete distribution, and compare the resulting statistics characterizing firing rates, spike-train irregularity, and correlation coefficy.Growing evidence suggests that excitatory neurons in the brain play a significant role in seizure generation. Nonetheless, spiny stellate cells are cortical excitatory non-pyramidal neurons in the brain, whose basic role in seizure occurrence is not well understood. In the present research, we study the critical role of spiny stellate cells or the excitatory interneurons (EI), for the first time, in epileptic seizure generation using an extended neural mass model inspired by a thalamocortical model originally introduced by another research group. Applying bifurcation analysis on this modified model, we investigated the rich dynamics corresponding to the epileptic seizure onset and transition between interictal and ictal states caused by EI connectivity to other cell types. Our results indicate that the transition between interictal and ictal states (preictal signal) corresponds to a supercritical Hopf bifurcation, and thus, the extended model suggests that before seizure onset, the amplitude and frequency of neural activities gradually increase. Moreover, we showed that (1) the altered function of GABAergic and glutamatergic receptors of EI can cause seizure, and (2) the pathway between the thalamic relay nucleus and EI facilitates the transition from interictal to ictal activity by decreasing the preictal period. Thereafter, we considered both sensory and cortical periodic inputs to study model responses to various harmonic stimulations. Bifurcation analysis of the model, in this case, suggests that the initial state of the model might be the main cause for the transition between interictal and ictal states as the stimulus frequency changes. The extended thalamocortical model shows also that the amplitude jump phenomenon and non-linear resonance behavior result from the preictal state of the modified model. These results can be considered as a step forward to a deeper understanding of the mechanisms underlying the transition from normal activities to epileptic activities.Linearized encoding models are increasingly employed to model cortical responses to running speech. Recent extensions to subcortical responses suggest clinical perspectives, potentially complementing auditory brainstem responses (ABRs) or frequency-following responses (FFRs) that are current clinical standards. However, while it is well-known that the auditory brainstem responds both to transient amplitude variations and the stimulus periodicity that gives rise to pitch, these features co-vary in running speech. Here, we discuss challenges in disentangling the features that drive the subcortical response to running speech. Cortical and subcortical electroencephalographic (EEG) responses to running speech from 19 normal-hearing listeners (12 female) were analyzed. Using forward regression models, we confirm that responses to the rectified broadband speech signal yield temporal response functions consistent with wave V of the ABR, as shown in previous work. Peak latency and amplitude of the speech-evoked brainstem response were correlated with standard click-evoked ABRs recorded at the vertex electrode (Cz). Similar responses could be obtained using the fundamental frequency (F0) of the speech signal as model predictor. However, simulations indicated that dissociating responses to temporal fine structure at the F0 from broadband amplitude variations is not possible given the high co-variance of the features and the poor signal-to-noise ratio (SNR) of subcortical EEG responses. In cortex, both simulations and data replicated previous findings indicating that envelope tracking on frontal electrodes can be dissociated from responses to slow variations in F0 (relative pitch). Yet, no association between subcortical F0-tracking and cortical responses to relative pitch could be detected. These results indicate that while subcortical speech responses are comparable to click-evoked ABRs, dissociating pitch-related processing in the auditory brainstem may be challenging with natural speech stimuli.Post-implantation localization of deep brain stimulation (DBS) lead based on a magnetic resonance (MR) image is widely used. Existing localization methods use artifact center method or template registration method, which may lead to a considerable deviation of > 2 mm, and result in severe side effects or even surgical failure. Accurate measurement of lead position can instantly inform surgeons of the imprecise implantation. This study aimed to identify the influencing factors in DBS lead post-implantation localization approach, analyze their influence, and describe a localization approach that uses the individual template method to reduce the deviation. We verified that reconstructing direction should be parallel or perpendicular to lead direction, instead of the magnetic field. Besides, we used simplified relationship between magnetic field angle and deviation error to correct the localization results. The mean localization error can be reduced after correction and favors the feasibility of direct localization of DBS lead using MR images. We also discussed influence of in vivo noise on localization frequency and the possibility of using only MR images to localize the contacts.The COVID-19 pandemic has produced alterations in the behaviour and psychological health of people, who have had to learn living under uncertain circumstances escaping their control. This situation has been aggravated in those countries applying strict home confinement rules to try bending their epidemic curve. This is the case of Spain, where the stringent lockdown period was extended over three months. This study aimed at proving a research hypothesis whereby living close to Green Infrastructure (GI) during the confinement period was beneficial for mental health. To this end, La Palma (Canary Islands) and Zaragoza (Peninsular Spain) were taken as case studies, since both locations distributed a questionnaire to address citizenry's self-reported mental health under strict lockdown conditions. A spatial statistical analysis of the responses collected by these questionnaires revealed that variables such as stress, anger, medication use, alcohol consumption or visits to the doctor significantly decreased if citizens were close to GI, whereas people having very high expectations of enjoying the city after the confinement were positively correlated to proximity of green areas. Although these outcomes are limited by the inferential capacity of correlation analysis, they point out to a sense of relief derived from having visual contact with vegetated landscapes and feeling stimulated about using them for recreation, aesthetical or sporting purposes. The joint consideration of these psychological gains with the social and environmental benefits provided by GI emphasizes the importance of approaching urban regeneration through the design and implementation of interconnected green spaces.
China has the largest number of smokers in the world. The great majority of China's smokers desire to quit smoking (QS); however, the success rate of self-quitting is low. This study investigated the effects of smoking cessation (SC) clinics in a cancer hospital in Hunan province and determined the influencing factors of successful SC.

Smokers were recruited to QS by healthcare workers in the SC clinic from February 2015 to February 2019. SC counseling was provided and telephone follow-up was conducted at 1 week, and at 1, 3 and 6 months. Patients who continued SC during the follow-up period were considered to have QS.

Of the 344 patients included in this study, 16.3% QS at one week, 26.5% at one month, 27.6% at three months, and 31.7% at six months. Age ≥60 years, previous SC attempts, immediate quit dates, and telephone follow-up times (3-4 calls) were predictive factors for smokers to SC at six months.

Age, previous attempts to QS, immediate quit dates and telephone follow-up times were independent predictors of SC success at six months. SC clinics and frequent telephone follow-up improve the success rate of SC, especially in patients who have previously tried to QS or in those who set immediate quit dates.
Age, previous attempts to QS, immediate quit dates and telephone follow-up times were independent predictors of SC success at six months. SC clinics and frequent telephone follow-up improve the success rate of SC, especially in patients who have previously tried to QS or in those who set immediate quit dates.
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